Role of multidetector computed tomography in the diagnosis and management of patients attending the rapid access chest pain clinic, The Scottish computed tomography of the heart (SCOT-HEART) trial: study protocol for randomized controlled trial.

BACKGROUND: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic. METHODS/DESIGN: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014. DISCUSSION: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01149590.

Renin-angiotensin system blockers are associated with reduced mortality and heart failure hospitalization in patients paced for complete atrioventricular block.

BACKGROUND: Right ventricular apical pacing can cause dyssynchronous activation of the ventricles, increase sympathetic activation, cause abnormalities in myocardial perfusion, worsen cardiac output and endothelial function, and may be associated with adverse cardiovascular effects. The use of rennin-angiotensin system blockers (RASBs) may be beneficial in counteracting these potentially harmful effects of right ventricular pacing. OBJECTIVE: To explore the impact of RASB use on the outcome in patients with right ventricular pacemakers implanted for complete atrioventricular (AV) block. METHODS: Patients implanted with right ventricular pacemakers for complete AV block between 1994 and 2009 were identified from the Tayside Pacing Registry. Cox proportional hazards model was used to assess differences in all-cause mortality and congestive heart failure hospitalizations for those receiving RASB during follow-up, adjusted for confounding variables. We also performed 2 sensitivity analyses--a propensity score-matched analysis and time-dependent analyses--to minimize bias. RESULTS: Eight hundred twenty patients (57% men; median age 73 years; range 22-103 years) received pacemakers for complete AV block between 1994 and 2008 (54% dual-chamber pacemaker and 46% ventricular demand pacemaker). Two hundred seventy-eight (34%) patients had received RASBs. Mean follow-up was 4.9 ± 4.6 years, with 540 (65%) deaths. RASB use was independently associated with significantly reduced mortality (adjusted hazard ratio 0.67; 95% confidence interval 0.47-0.94; P = .017) and reduced heart failure hospitalization (adjusted hazard ratio 0.42; 95% confidence interval 0.17-0.92; P <.001). CONCLUSIONS: This study suggests that RASBs may confer outcome benefits in patients with right ventricular pacemakers implanted for complete AV block.

Pulmonary hypertension predicts all-cause mortality in patients with heart failure: a retrospective cohort study.

AIMS: The presence of pulmonary hypertension (PH) in left ventricular systolic dysfunction (LVSD) and symptomatic heart failure is an ominous sign. There are insufficient data regarding the risk conferred by increasing severity of PH in patients with heart failure. METHODS AND RESULTS: We performed a record linkage study in Tayside, Scotland (population ∼400,000) utilizing the Tayside echocardiogram database (>50,000 echocardiograms) maintained by the Health Informatics Centre (HIC). Data sets from the HIC include mortality data, cardiovascular medications, and other healthcare activities linked anonymously by the community health index (CHI) number. Patients were included in the analysis if they had LVSD, had a valid right ventricular systolic pressure (RVSP) measurement, and had a loop diuretic prescription (provided not more than 1 year prior to echocardiogram). A Cox proportional hazard model was used to examine the effects of RVSP on all-cause mortality. A total of 1612 patients [mean age, 75.2 ± 10.9 (SD) years; 57.4% male] met the entry criteria. Mean RVSP for the cohort was 44.9 ± 13.1 mmHg and mean follow-up was 2.8 ± 2.5 years. For each 5 mmHg stepwise increase in RVSP, after adjustment for confounding factors including the degree of LVSD and the presence of chronic obstructive pulmonary disease, the hazard ratio (HR) for all-cause mortality was 1.06 (1.03-1.08, P < 0.001). CONCLUSIONS: Pulmonary hypertension predicted all-cause mortality in a heterogeneous group of patients with heart failure. Each 5 mmHg rise in RVSP was associated with a 6% increased risk of death.

The impact of renin-angiotensin-aldosterone system blockade on heart failure outcomes and mortality in patients identified to have aortic regurgitation: a large population cohort study.

OBJECTIVES: The aim of this study was to investigate the effect of renin-angiotensin system blockade on outcomes in patients with aortic regurgitation (AR). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have the potential to reduce afterload, blunt left ventricular wall stress, and limit left ventricular dilation and hypertrophy. However, long-term studies have yielded inconsistent results, and very few have assessed clinical outcomes. METHODS: The Health Informatics Centre dispensed prescription and morbidity and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database. Patients diagnosed with at least moderate AR from 1993 to 2008 were identified. Cox regression analysis was used to assess differences in all-cause mortality and cardiovascular (CV) and AR events (heart failure hospitalizations, heart failure deaths, or aortic valve replacement) between those treated with and without ACE inhibitors or angiotensin receptor blockers (ARBs). RESULTS: A total of 2,266 subjects with AR (median age 74 years; interquartile range: 64 to 81 years) were studied, with a mean follow-up period of 4.4 ± 3.7 years. Seven hundred and five patients (31%) received ACE inhibitor or ARB therapy. There were 582 all-cause deaths (25.7%). Patients treated with ACE inhibitors or ARBs had significantly lower all-cause mortality and fewer CV and AR events, with adjusted hazard ratios of 0.56 (95% confidence interval [CI]: 0.64 to 0.89; p < 0.01) for all-cause mortality, 0.77 (95% CI: 0.67 to 0.89; p < 0.01) for CV events, and 0.68 (95% CI: 0.54 to 0.87; p < 0.01) for AR events. CONCLUSIONS: This large retrospective study shows that the prescription of ACE inhibitors or ARBs in patients with moderate to severe AR was associated with significantly reduced all-cause mortality and CV and AR events. These data need to be confirmed by a prospective randomized controlled outcome trial.

Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis.

OBJECTIVES: The purpose of this study was to investigate the impact of renin-angiotensin system blockade therapy on outcomes in aortic stenosis (AS). BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are perceived to be relatively contraindicated in AS. However, inhibitors of the renin-angiotensin system may be beneficial in AS through their cardioprotective and beneficial effects on left ventricular remodeling. METHODS: The Health Informatics dispensed prescribing, morbidity, and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database (>110,000 scans). Patients with a diagnosis of AS from 1993 to 2008 were identified. Cox regression model (adjusted for confounding variables) and propensity score analysis were used to assess the impact of ACEIs or ARBs on all-cause mortality and cardiovascular (CV) events (CV death or hospitalizations). RESULTS: A total of 2,117 patients with AS (mean age 73 ± 12 years, 46% men) were identified and 699 (33%) were on ACEI or ARB therapy. Over a mean follow-up of 4.2 years, there were 1,087 (51%) all-cause deaths and 1,018 (48%) CV events. Those treated with ACEIs or ARBs had a significantly lower all-cause mortality with an adjusted hazard ratio of 0.76 (95% confidence interval: 0.62 to 0.92, p < 0.0001) and fewer CV events with an adjusted hazard ratio of 0.77 (95% confidence interval: 0.65 to 0.92, p < 0.0001). The outcome benefits of ACEIs/ARBs were further supported by propensity score analysis. CONCLUSIONS: This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS.

Validity of self-reported smoking status: Comparison of patients admitted to hospital with acute coronary syndrome and the general population.

Many studies rely on self-reported smoking status. We hypothesized that patients with acute coronary syndrome (ACS), a smoking-related condition, would be more prone to misclassify themselves as ex-smokers, because of pressure to quit. We compared patients admitted with ACS with a general population survey conducted in the same country at a similar time. We determined whether ACS patients who classified themselves as ex-smokers (n = 635) were more likely to have cotinine levels suggestive of smoking deception than self-reported ex-smokers in the general population (n = 289). On univariate analysis, the percentage of smoking deceivers was similar among ACS patients and the general population (11% vs. 12%, p = .530). Following adjustment for age, sex and exposure to environmental tobacco smoke, ACS patients were significantly more likely to misclassify themselves (adjusted OR = 14.06, 95% CI 2.13-93.01, p = .006). There was an interaction with age whereby the probability of misclassification fell significantly with increasing age in the ACS group (adjusted OR = 0.95, 95% CI 0.93-0.97, p<.001), but not in the general population. Overall, smoking deception was more common among ACS patients than the general population. Studies comparing patients with cardiovascular disease and healthy individuals risk introducing bias if they rely solely on self-reported smoking status. Biochemical confirmation should be undertaken in such studies.

Spironolactone has antiarrhythmic activity in ischaemic cardiac patients without cardiac failure.

OBJECTIVES: To examine whether endogenous aldosterone can cause either arrhythmias (and some of their underlying mechanisms) or endothelial dysfunction in patients with coronary artery disease (CAD) but without heart failure. BACKGROUND: Aldosterone blockade has been shown to reduce the incidence of sudden death in patients with heart failure. This could be caused by a reduction in arrhythmias or in coronary events. Whether either effect also occurs in other cardiac patients without heart failure is currently unknown. METHOD: We performed a randomized, placebo-controlled, double-blind crossover study on 98 patients with CAD but without heart failure on standard therapy, comparing 12.5-50 mg/day spironolactone (3 months) with placebo. Endothelial function was assessed by bilateral forearm venous occlusion plethysmography. Ventricular extrasystoles, procollagen III N-terminal peptide (PIIINP) and QT interval length were used to represent arrhythmias and their determinants. RESULTS: Spironolactone produced a highly significant 75% reduction in ventricular extrasystoles (median 192, range 48-744) on placebo compared with spironolactone (median 48, range 19.2-288, P < 0.003). Spironolactone also decreased the QT interval from a mean of 440 +/- 28 to a mean of 425 +/- 25 (P < 0.001) and a collagen marker (PIIINP) from a mean of 3.6 +/- 0.9 to a mean of 3.0 +/- 0.8 (P < 0.001), but did not significantly change endothelial dysfunction or heart rate variability. CONCLUSION: These results suggest that despite conventional therapy, endogenous aldosterone can be an arrhythmogenic influence in patients with CAD, but without heart failure. The possible mechanisms are that aldosterone promotes myocardial fibrosis and lengthens the QTc interval as well as decreasing potassium in CAD patients without heart failure.

The cardiovascular risk factor, left ventricular hypertrophy, is highly prevalent in stable, treated angina pectoris.

BACKGROUND: In coronary artery disease (CAD), a potentially reversible factor leading to cardiac death is left ventricular hypertrophy (LVH). However, LVH will only have a large impact overall in CAD if it is highly prevalent. Therefore we aimed to assess the prevalence of LVH in patients with stable, treated angina and its relationship with blood pressure (BP). METHODS: Three hundred twenty-two consecutive patients with angiographically confirmed coronary artery disease were recruited. Echocardiographic LV mass was performed and correlated with both office and 24-h ambulatory BP. RESULTS: Of the 267 patients with LV mass measurements, 195 (73%) had LVH. The mean 24-h ambulatory BP reading was systolic 125 +/- 12 mm Hg and diastolic 68 +/- 8 mm Hg in the LVH group. Of the LVH patients 62% had a nonhypertensive 24-h BP reading. On multivariate logistic regression analysis, factors independently related to LVH were history of hypertension (odds ratio [OR] 1.848, 95% confidence interval [CI] 1.051-3.248), body mass index (OR 1.085, 95% CI 1.011-1.165), and age (OR 1.039, 95% CI 1.004-1.076). CONCLUSIONS: We conclude that echo LVH is very common in patients with stable, treated angina and the majority of these patients had a nonhypertensive BP at the time of study. Studies are now required to determine whether identifying and vigorously treating LVH in CAD would reduce the risk of premature death in these patients.

Screening for left ventricular systolic dysfunction using GP-reported ECGs.

BACKGROUND: Diagnostic echocardiography has poor access for patients with suspected heart failure. Pre-echocardiography screening with electrocardiograms (ECGs) is recommended as a means of targeting this scarce resource. There are data to support this policy when ECGs are interpreted by cardiologists but not by GPs. AIM: To assess the value of GP-reported ECGs as a pre-echocardiography screening test for left ventricular systolic dysfunction (LVSD). DESIGN OF STUDY: Cross-sectional study of GPs' ECG reporting skills. SETTING: General practice, NHS in Scotland. METHOD: A randomly selected, stratified sample of 123 Scottish GPs reviewed 180 ECGs (100 abnormal, 50 normal and 30 duplicate) from 150 patients with suspected heart failure. Forty-one patients had LVSD on echocardiography. GPs were required to categorise ECGs as normal or abnormal. RESULTS: Mean sensitivity was 0.94 (95% CI = 0.92 to 0.95). Mean specificity 0.58 (95% CI = 0.56 to 0.60). Mean positive predictive value (PPV) was 0.47 (95% CI = 0.46 to 0.48). Mean negative predictive value (NPV) was 0.96 (95% CI = 0.95 to 0.97). Mean likelihood ratio was 2.39 (95% CI = 2.28 to 2.50). Seventy of 123 (57%) GPs achieved sensitivity of 0.9 and specificity of 0.5 for the detection of LVSD. CONCLUSION: Most Scottish GPs have the skills to perform pre-echocardiography screening ECGs in patients with suspected LVSD. However, differences in ECG reporting performance between individual GPs will result in widely varying referral rates for echocardiography and differences in the detection rate of LVSD. The implications of these findings need to be considered when heart failure diagnostic services are being developed.

A critical re-appraisal of different ways of selecting ambulatory patients with suspected heart failure for echocardiography.

BACKGROUND: ECG and BNP have been assessed as screening tests for LVSD and heart failure. However, echocardiography also provides information about valvular disease and LVH. We assessed how good these screening tests are in identifying whether the subsequent echocardiogram will have any significant abnormality. AIMS: To re-appraise the ECG and BNP as screening tests for echocardiography since there are important practical deficiencies in our current knowledge in this area. METHODS: General practitioners referred suspected heart failure patients for clinical assessment, echocardiography, electrocardiography, and BNP measurement. The accuracy of each screening test and combinations of screening tests were calculated for LVSD, heart failure, valvular disease, and LVH. RESULTS: The sensitivities of the ECG for LVSD, heart failure, LVH and valvular disease were 97%, 95%, 76%, and 69%, respectively. The corresponding figures for BNP were 86%, 82%, 59%, and 48%, respectively. When patients with atrial fibrillation and murmurs were excluded, the values for ECG were 94%, 87%, 53%, and 55%, while for BNP they were 83%, 73%, 50%, and 32%. CONCLUSIONS: ECG interpretation and BNP are adequate screening tests to detect LVSD or heart failure but fail to screen for other echocardiographic abnormalities, like valvular disease and LVH. This remains the case even if patients with atrial fibrillation or heart murmurs are excluded on the basis that they require echocardiography anyway.

Infective endocarditis presenting with Parinaud's dorsal midbrain syndrome.

We present a case of vertical gaze palsy in a 13-year-old girl caused by underlying infective endocarditis, secondary to an infected navel piercing. This case illustrates that infective endocarditis does not always present with classic signs.

How much echo left ventricular hypertrophy would be missed in diabetics by applying the Losartan Intervention For Endpoint Reduction electrocardiogram criteria to select patients for angiotensin receptor blockade?

OBJECTIVE: The Losartan Intervention For Endpoint Reduction (LIFE) study demonstrated a clear mortality benefit in treating hypertensive patients with electrocardiogram (ECG) evidence of left ventricular hypertrophy (LVH) with losartan rather than atenolol. Previous studies have also shown that identifying and treating echo LVH is associated with prognostic benefits in hypertensive subjects, and is independent of the presence of ECG LVH. We sought to determine how many cases of echo LVH would be missed by applying the ECG criteria for LVH used in the LIFE study. DESIGN: A prospective study of 219 patients with type 2 diabetes recruited from the hospital diabetic clinic. METHODS: Fifteen ECG criteria were assessed on each subject and compared with the presence or absence of LVH on echocardiography. RESULTS: All the proposed ECG criteria are poor at identifying echo LVH in people with diabetes. CONCLUSION: Using ECG LVH to select patients for angiotensin receptor blockade would lead to many diabetics with echo LVH missing out on the benefits of treatment. This assumes that the benefits seen in the LIFE study would also occur if the LIFE strategy were extended to echo LVH patients as well as to ECG LVH patients.

Relation of QT interval dispersion to the number of different cardiac abnormalities in diabetes mellitus.

Three studies have clearly shown that a prolonged QT dispersion (QTD) is the best predictor of cardiac death in patients with type 2 diabetes mellitus (DM). This was originally believed to be because QTD identified electrical inhomogeneity, but recent data suggests that this is unlikely. The alternative possibility is that QTD is a convenient identifier of hidden but lethal cardiac abnormalities. We explored whether the latter possibility is true by examining exactly what spectrum of cardiac abnormalities, if any, are over-represented in diabetics with a prolonged QTD. Two hundred nineteen patients with type 2 DM who had been first diagnosed with DM 3 to 6 years previously underwent intensive cardiac examinations. Patients with prolonged QTD had a significantly increased incidence of myocardial ischemia and left ventricular (LV) hypertrophy, and to a lesser extent, autonomic dysfunction. The main independent determinant of a prolonged QTD was ischemia, as seen on both ambulatory ST-segment monitoring (p <0.001) and Duke score on treadmill testing (p <0.001). It was also observed that QTD increased progressively as the number of different cardiac abnormalities increased (p <0.001). These studies suggest that QTD is a useful, general prescreening test to select diabetics for more detailed cardiac examinations (especially for ischemia and LV hypertrophy), and that if cardiac examinations were targeted by way of QTD screening, then a high incidence of hidden but treatable cardiac abnormalities could be found.

Is glutamine beneficial in ischemic heart disease?

OBJECTIVE: Glutamine enhances recovery from acute normothermic ischemia in isolated rat heart by a dose-dependent effect (Khogali et al. J Mol Cell Cardiol 1998;30:819). We compared the cardioprotective effects of equimolar concentrations of glutamine, glutamate, and aspartate in isolated rat heart. We also explored the potential cardioprotective effects of glutamine in patients with chronic stable angina. METHODS: The isolated perfused working rat heart was subjected to ischemia, followed by reperfusion with or without an amino acid (2.5 mM). Patients with chronic stable angina received a single oral dose of glutamine (80 mg/kg) or placebo in a double-blind, random fashion 40 min before a standard Bruce exercise test. RESULTS: Postischemic reperfusion of isolated rat heart with glutamine (but not with glutamate or aspartate) resulted in full recovery of cardiac output. Only glutamine prevented the decrease in the myocardial ratio between adenosine triphosphate to adenosine diphosphate and significantly enhanced the myocardial ratio of reduced to oxidized glutathione. A single oral dose of glutamine given to patients with chronic stable angina significantly increased plasma glutamine concentration from 419 to 649 microM and delayed time to onset of more than 1.0 mm of ST segment depression on the ECG by 38 s. CONCLUSION: Glutamine may be cardioprotective in patients with coronary heart disease.